Trypanocidal and leishmanicidal activities of flavonoids from Argentine medicinal plants.

In vitro trypanocidal and leishmanicidal activities of the flavonoids hispidulin, from Ambrosia tenuifolia, and santin, from Eupatorium buniifolium, are reported. A sensitive technique that takes advantage of ((3)H)thymidine uptake by dividing trypanosomatids has been adjusted for quantification of the parasiticidal effect of the natural products. The IC(50) values for hispidulin and santin on Trypanosoma cruzi epimastigotes were 46.7 and 47.4 muM, respectively. On trypomastigotes, the IC(50) values were 62.3 microM for hispidulin and 42.1 microM for santin. Hispidulin was more active than santin on promastigotes of Leishmania mexicana (IC(50) = 6.0 microM versus 32.5 microM). No cytotoxic activity was observed on lymphoid cells, making hispidulin and santin potential lead compounds for the development of new natural drugs. This is the first report on the trypanocidal and leishmanicidal activities of these flavonoids and on the presence of santin in E. buniifolium.

Tilia cordata Mill. Extracts and scopoletin (isolated compound): differential cell growth effects on lymphocytes.

Aqueous extracts or infusions obtained from the flowers of Tilia species are widely used for the treatment of anxiety in folk medicine. In this work, the antiproliferative action of aqueous, dichloromethane and ethanol extracts obtained from Tilia cordata Mill. flowers on tumoral (BW 5147 lymphoma) and normal lymphocytes is described. Both extracts showed a selective action on tumoral cells, inducing apoptosis. In the case of normal T cells these extracts suppressed mitogen-induced proliferation without affecting viability, suggesting a suppressive but not cytotoxic effect. These effects were clearly concentration dependent. A coumarin (scopoletin), the main component in the dichloromethane extract presented antiproliferative action on BW 5147 cells, suggesting that it may be at least partly responsible for the activity displayed by this extract.

Antioxidant and free radical scavenging activities of Misodendrum punctulatum, myzodendrone and structurally related phenols.

The peroxyl radical scavenging activity of a dry methanol extract of Misodendrum punctulatum was determined by means of luminol-enhanced chemiluminescence assay, allowing to calculate the total reactive antioxidant potential (TRAP) index equal to 239 +/- 26 microm, expressed in Trolox equivalents. The flavan-3-ol catechin (1) and the phenylbutanone derivative myzodendrone (2) were identified through assay-guided fractionation as active metabolites present in the extract, and their structures were elucidated by chemical and spectroscopic analysis. Three other structurally related synthetic phenols, dehydrozingerone (3), zingerone (4) and myzodendrone aglycone (5), were also analysed using this method. Compounds 1 and 2 were highly effective as free radical scavengers (TRAP = 1257 microm and 1018 microm, respectively) when compared with Trolox (TRAP = 144 microm), used as a standard. Compounds 3 and 5 were also active showing TRAP values of 229 microm and 219 microm, respectively, similarly to that observed for the dry extract. On the other hand, 4 was inactive. Catechin (1) also reduced the production of thiobarbituric acid reactive substances (TBARS) in rat liver homogenates, with IC50 = 26 microg/mL, superior to that obtained for Trolox, IC50 = 73 microg/mL. Compounds 2 and 5 showed IC50 values > 1000 microg/mL, while no activity could be observed for 3, 4, or the extract.

Effect of Larrea divaricata Cav. extract and nordihydroguaiaretic acid upon peroxidase secretion in rat submandibulary glands.

Free radicals are involved in several diseases, including cancer, central nervous system alterations and inflammatory pathologies. Peroxidase is an oral enzyme implicated in the defence of oral cavity. It has been determined that flavonoids and lignans possess antioxidant and free radical scavenging either directly or indirectly, usually by means of increasing the secretion of free radicals scavenger enzymes. Larrea divaricata Cav. is a plant used in folk Argentine medicine for the treatment of cancer and inflammatory ailments. In this study, we have determined the effect and mechanism of action of an aqueous extract of the leaves of L. divaricata and NDGA on peroxidase secretion in female rat submandibular glands. The extract significantly increased the secretion and total peroxidase. % of secreted peroxidase (X +/- S.E.M.): extract maximum response: 150 +/- 10; % of total peroxidase (X +/- S.E.M.): extract maximum response: 1000 +/- 90. The effect of the extract on peroxidase secretion was mediated by beta1 adrenoceptors (% of secreted peroxidase: extract + atenol maximum response: 50 +/- 4 ). Meanwhile, NDGA produced a decrease in peroxidase secretion (peroxidase secreted: basal: 0.44 +/- 0.03; NDGA 2.5 x 10(-6) M: 0.20 +/- 0.02; prostaglandins E2 (PGE2) 10(-7)M: 1.32 +/- 0.5; NDGA + PGE2: 0.46 +/- 0.035), an effect that was exerted by the inhibition on prostaglandins synthesis.

Anti-Trypanosoma cruzi activity of green tea (Camellia sinensis) catechins.

The trypanocidal action of green tea catechins against two different developmental stages of Trypanosoma cruzi is reported for the first time. This activity was assayed with the nonproliferative bloodstream trypomastigote and with the intracellular replicative amastigote parasite forms. An ethyl acetate fraction from Camellia sinensis green tea leaves, which contains most of the polyphenolic compounds and the maximal trypanocidal activity, was obtained by fractionation of the aqueous extract with organic solvents. The active compounds present in this extract were further purified by LH-20 column chromatography and were identified by high-performance liquid chromatography analysis with a photo diode array detector and gas chromatography coupled to mass spectroscopy. The following flavan-3-ols derivatives, known as catechins, were identified: catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, and epigallocatechin gallate. The purified compounds lysed more than 50% of the parasites present in the blood of infected BALB/c mice at concentrations as low as 0.12 to 85 pM. The most active compounds were gallocatechin gallate and epigallocatechin gallate, with minimal bactericidal concentrations that inhibited 50% of isolates tested of 0.12 and 0.53 pM, respectively. The number of amastigotes in infected Vero cells decreased by 50% in the presence of each of these compounds at 100 nM. The effects of the catechins on the recombinant T. cruzi arginine kinase, a key enzyme in the energy metabolism of the parasite, were assayed. The activity of this enzyme was inhibited by about 50% by nanomolar concentrations of catechin gallate or gallocatechin gallate, whereas the other members of the group were less effective. On the basis of these results, we suggest that these compounds could be used to sterilize blood and, eventually, as therapeutic agents for Chagas' disease.